Sugar-Assisted Kinetic Resolution of Amino Acids and Amplification of Enantiomeric Excess of Organic Molecules: Homochirality

The origins of biological homochirality have intrigued researchers since Pasteur’s discovery of the optical activity of biomolecules. In 2004, we proposed and soon thereafter disclosed a novel alternative for the evolution of homochirality that is not based on autocatalysis and forges a direct relationship between the chirality of sugars and amino acids.1,2 This process provides a mechanism in which a racemic mixture of an amino acid can catalyze the formation of an optically active organic molecule such a sugar in the presence of a sugar of low enantiomeric excess. Where glyceraldehyde being the simplest sugar playing a crucial role. The synergistic and intrinsic relationship between sugars and amino acids via kinetic resolution were discovered in the amino acid-catalyzed neogenesis of carbohydrates were we observed significant amplification of enantiomeric excess.3 The mechanism involves interconnected catalytic cycles were dynamic kinetic resolution and diastereoselective interactions between the catalyst and the chiral sugar or amino acid product are fundamental for amplifying of a single enantiomer and diasteriomer of multiple possible stereochemical outcomes..1-6 The sugar-assisted kinetic resolution of amino acids can also be observed and applied to asymmetric synthesis.2-8 Here the synergistic interplay between the chiral sugar substrate (e.g. glyceraldehyde, ribose) and the chiral amino acid derivative allowed for the construction of a functionalized sugar product with high enantioselectivity (up to 99 %) also when using a combination of racemic amine catalyst (0 % ee).7

The symbiotic behavior of sugars and amino acids, in combination with the likely presence of each in the prebiotic milieu, suggests that their
cooperative action could have contributed to the early achievement of highly enantioenriched products under prebiotic conditions and may be an explanation for the origin of homochirality where the initial asymmetry may have been set by an amino acid or sugar.

  1. Córdova, A.; Sundén, H.; Xu, Y.; Ibrahem. I.; Zou, W.; Engqvist, M. Chem Eur. J. 2006, 12, 5446. Sugar assisted kinetic resolution of amino acids and amplification of enantiomeric excess of organic molecules. https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.200600526
  2. Córdova, A. American Institute of Physics. 2008, 979, 47. Asymmetric amino acid catalysis.
  3. Córdova, A.; Engqvist, M.; Ibrahem, I.; Casas, J.; Sundén, H. Chem. Commun. 2005. 2047. Plausible origins of homochirality in the amino acid catalyzed neogenesis of carbohydrates. https://pubs.rsc.org/en/content/articlelanding/2005/cc/b500589b
  4. Reyes, E.; Córdova, A. Tetrahedron Letters. 2005, 46, 6605. Amino acid-catalyzed carbohydrate synthesis by dynamic kinetic asymmetric transformations (DYKAT).
  5. Rios, R.; Schyman, P.; Sundén, H.; Zhao, G.-L.; Ullah, F.; Chen, L.; Laaksonen, A.; Córdova, A. Chem. Eur. J. 2010, 16, 13935. Nonlinear Effects in Asymmetric Amino Acid Catalysis by Multiple Interconnected Stereoselective Catalytic Networks.
  6. Ibrahem, I.; Sundén, H.; Dziedzic, P.; Rios, R.; Córdova, A. Adv. Synth. Cat. 2007, 349, 1868. Asymmetric Amplification in the Amino Acid-Catalyzed Amino Acid Synthesis.
  7.  Zhang, K.; Carmo, C.; Deiana, L.; Svensson Grape, E.; Inge, K. A.; Córdova, A. Chem. Eur. J 2023, 29, e202301725 Sugar-assisted Kinetic Resolutions in Metal/Chiral Amine Co-catalyzed α-Allylations and [4+2] Cycloadditions: Highly Enantioselective Synthesis of Sugar and Chromane Derivatives 
  8. Zhang, K.; Wu, H.; Inge, A. K.; Córdova, A. Adv. Synth. Catal. 2024, 366, 2370. Direct catalytic stereoselective synthesis of C4’ functionalized furanoside and nucleoside derivatives with a tetrasubstituted stereocenter. https://doi.org/10.1002/adsc.202301509